Prophylactic Bactericidal Medical Device

ABSTRACT

A medical implant system is described for inhibiting infection associated with a joint prosthesis implant. An inventive system includes an implant body made of a biocompatible material which has a metal component disposed on an external surface of the implant body. A current is allowed to flow to the metal component, stimulating release of metal ions toxic to microbes, such as bacteria, protozoa, fungi, and viruses. One detailed system is completely surgically implantable in the patient such that no part of the system is external to the patient while the system is in use. In addition, externally controlled devices are provided which allow for modulation of implanted components.

REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. patent application Ser. No.11/172,138, filed Jun. 30, 2005 and U.S. Provisional Patent ApplicationSer. No. 60/708,320, filed Aug. 15, 2005, the entire content of each ofwhich is incorporated herein by reference.

FIELD OF THE INVENTION

The invention relates to systems and methods for inhibition of microbialinfection related to surgical implant devices. In particular, theinvention relates to systems and methods for inhibition of microbialinfection related to orthopedic implants.

BACKGROUND OF THE INVENTION

Joint degeneration is the leading chronic condition in the elderly; itaffects one in every eight Americans and almost half the population overthe age of 65. (Brooks, P. M, Med. J. Aust., 173:307-308, 2000) The mostcommon form of joint degeneration is osteoarthritis. Osteoarthritisweakens and breaks down cartilage and bone, causing pain as bones rubtogether. Eventually the constant rubbing of the bony surfaces destroysthe surfaces that are rubbing against one another leading to rough,painful movement. Total joint replacement, or arthroplasty, represents asignificant advance in the treatment of painful and disabling jointpathologies. Arthroplasty can be performed on almost any joint of thebody including the hip, knee, ankle, foot, shoulder, elbow, wrist, andfingers. Total joint replacement: whether hip, knee, ankle, foot,shoulder, elbow, wrist, and fingers or other, is typically done as afinal stage treatment for a patient who suffers from some form of jointdegeneration.

In its early stages, many people manage arthritis pain conservatively byusing anti-inflammatory medicines, weight reduction, lifestylemodification, physiotherapy, or occupational therapy. However, as thedisease progresses the pain intensifies. When the pain gets to the pointwhere everyday, normal activities such as putting on shoes and socks orwalking up stairs become too painful, total joint replacement surgery isan attractive option to restore movement and independence, and todramatically reduce pain.

Although joint replacement is a relatively large field withinorthopedics, the number of fracture fixation devices utilized around theworld far outranks the number of artificial joints. Fracture fixation isgrowing daily as the number of fractures associated with traumaaccidents is increasing. Fixation devices can be internal or external innature and include devices such as a plate, wire, screw, pin, rod, nailor staple, which aid in maintaining fracture fragments in properposition during healing. Such devices are usually inserted after openreduction of the fracture and will remain for the entirety of thehealing process, often becoming a permanent structure within the body.

Joint replacement surgery began in the early 1950's, and its frequencyhas grown as surgical techniques and medical care associated withsurgery improves. In the late 1980's between 500,000 and 1 million totalhip replacements were performed per year, while in 2004 it is estimatedthat approximately 600,000 joint prosthesis and 2,000,000fracture-fixation devices will be inserted into patients in the UnitedStates.

Unfortunately, as the number of implant surgeries increases, the numberof associated infections also increases. Any person who has an implantis at risk for developing an infection associated with the device. It isestimated that 2 percent of joint prostheses and 5 percent of fixationdevices will become infected. Taking 3 percent as an average estimate ofinfected implants, as many as 30 million incidents of infection mayoccur.

The effects of implant infection are expensive as well as a danger tothe health and well-being of the affected individual. For example,infection results in direct medical and surgical costs and additionallymay cause patient pain, suffering, lost wages, lost work and decreasedproductivity. On average an infected hip prosthesis patient spends sixtimes the number of days in the hospital when compared to thenon-infected prosthetic hip patient. In 1991, the total cost of aninfected patient, both in hospital and as an outpatient, was $45,000 ascompared to the total cost of $8,600 associated with a non-infectedpatient. (Bengston, S., Ann. Med., 25:523-529, 1993)

Joint replacement implants and fixation devices include a variety ofmaterials foreign to the human body, such as metals, plastics, andpolymeric substances, all of which have the potential to serve assubstrates for attachment and growth of microorganisms.

In particular, certain microorganisms may exude a glycocalyx layer thatprotects certain bacteria from phagocytic engulfment by white bloodcells in the body. The glycocalyx also enables some bacteria to adhereto environmental surfaces (metals, plastics, root hairs, teeth, etc.),colonize, and resist flushing.

Once microorganisms colonize an implant, it is often very difficult toeradicate or even inhibit the infection. For example, systemicadministration of antibiotics is often ineffective due to limited bloodsupply to the areas of the implant. Additionally, many bacterial speciestoday are resistant to antibiotics.

Where infection cannot be inhibited it may spread and become even moreserious, as in patients who have an infection within the bone,osteomyelitis. Such patients often must undergo a difficult and costlytreatment involving extended hospitalization, joint debridement,aggressive antimicrobial therapy, total joint removal followed by totaljoint replacement and possible amputation if the infection can not beeliminated.

Since implantation of an orthopedic implant device, such as a jointreplacement prosthesis or fixation device, is quite common andassociated infection frequent, there is a continuing need for newapproaches to inhibition of infection. In particular, it would be verydesirable for both the physician as well as the patient to be able totreat a prosthetic osteomyelitic infection without the removal of animplant. Further, economical and safe apparatus and methods ofinhibiting implant associated infections are needed.

SUMMARY OF THE INVENTION

A medical implant system includes an implant body made of abiocompatible material. The implant body has an external surface and ametal component containing an antimicrobial metal is disposed on theexternal surface of the implant body. A medical implant system accordingto the present invention includes a power source having a first terminaland a second terminal and further includes an insulator placed in acurrent path between the first terminal of the power source and thesecond terminal of the power source preventing current flowing from thefirst terminal from reaching the second terminal without completing acircuit including a conductive body tissue or fluid adjacent to theexternal surface of the implant system when implanted.

A medical implant system according to the present invention may beconfigured as any of various types of implant. Optionally, an implantbody is a joint replacement prosthetic implant. In a further option animplant body is a part of a joint replacement prosthetic implant. Animplant body may also be an orthopedic fixation device, an orthopedicspacer, or a combination of a joint replacement prosthetic implant, anorthopedic fixation device, or an orthopedic spacer.

More than one implant body may be included as part of an inventivesystem. In addition, more than one power source may be provided, forexample, where more than one implant body is included.

In a highly preferred embodiment, a medical implant system is providedhaving an implant body which includes a first element having a firstexternal surface and a second element having a second external surface,as well as a first metal component containing an antimicrobial metalwhich is disposed on at least the first external surface of the implantbody. A power source having a first terminal and a second terminal isincluded in an inventive implant and the first terminal is in electricalcommunication with the first metal component. The second terminal is inelectrical communication with the second external surface. An insulatoris placed in a current path between the first terminal of the powersource and the second terminal of the power source preventing currentflowing from the first terminal from reaching the second terminalwithout completing a circuit including a conductive body tissue or fluidadjacent to the external surface of the implant system when implanted.

In a preferred option, a second metal component containing anantimicrobial metal is disposed on the second external surface, and thesecond terminal is in electrical communication with the second metalcomponent. In such a configuration, the insulator insulates the firstmetal component from the second metal component.

In one embodiment, an internal cavity having a wall and an opening isincluded in the implant body and a cap is provided to close the openingof the internal cavity. A power source is positioned in the internalcavity.

In one embodiment of the present invention, a portion of the cap incontact with the wall of an internal cavity includes an electricallyinsulating material preventing current flowing from the first terminalof the power source from reaching the second terminal of the powersource without completing a circuit including a conductive body tissueor fluid adjacent to the external surface of the implant system whenimplanted. For example, at least a portion of the cap in contact withthe wall of an internal cavity may be made of an insulating material ormay have a coating of an insulating material, forming an insulatingregion. The insulating region may extend a distance from the region ofcontact with the wall. However, it is appreciated that a cap optionallyprovides a current path from an external surface to a power sourceterminal, and therefore, the cap may provide such a current path inregions of the cap away from contact with the wall.

A medical implant system is provided according to an embodiment of thepresent invention which includes an implant body having a main bodyportion having a first external surface and a cap portion having asecond external surface. An antimicrobial metal-containing coating, suchas a silver-containing coating, is disposed on the first externalsurface of the main body portion. A power source having a first terminaland a second terminal is provided as part of an inventive system, thefirst terminal of the power source is in electrical communication withthe silver-containing coating and the second terminal is in electricalcommunication with the second external surface. An insulator is placedin a current path between the first terminal of the power source and thesecond terminal of the power source preventing current flowing from thefirst terminal from reaching the second terminal without completing acircuit including a conductive body tissue or fluid adjacent to theexternal surface of the implant system when implanted. An internalcavity is present in the implant body and the power source is disposedtherein. The internal cavity and power source may be positioned at anyconvenient position. In a preferred embodiment, the internal cavity isin the main body portion. Alternatively, an intermediate portion havingan internal cavity may be provided and attached to the main body portionand the cap.

In a specific embodiment, a cap is provided which includes a protrudingportion, the internal cavity comprises a threaded surface and theinsulator comprises a screw thread insert, and wherein the protrudingportion of the cap interacts with the screw thread insert to form a maleconnector for reciprocal interaction of the threaded surface of theinternal cavity and the male connector.

A medical implant system is provided in the form of an orthopedicfixation device in one embodiment. An inventive device includes asupport structure for supporting at least two orthopedic fixators. Thesupport structure is adapted to secure the at least two orthopedicfixators to the support. A first orthopedic fixator supported by thesupport structure has a first external surface and a second orthopedicfixator supported by the support structure has a second externalsurface. A first metal component containing an antimicrobial metal isdisposed on the first external surface of the first fixator. A powersource having a first terminal and a second terminal is included and thefirst terminal is in electrical communication with the first metalcomponent. An insulator is disposed on the support structure in acurrent path between the first terminal of the power source and thesecond terminal of the power source preventing current flowing from thefirst terminal from reaching the second terminal without completing acircuit including a conductive body tissue or fluid adjacent to theexternal surface of the first fixator when implanted.

In a preferred option, the implant is adapted to be disposed totallywithin a human body when in use as an implant. Thus, for example, nowires or other conductive elements protrude from the body of anindividual having an inventive implant. In the case of an orthopedicfixation device, certain embodiments include a support structure, powersource and/or a portion of a fixator present outside the body of apatient when at least a portion of the fixator is implanted.

Also optionally, a current conductor, such as a metal component, isdisposed on a portion of the internal cavity wall, preferably such thatthe portion of the metal component in the cavity is continuous with theportion of the metal component disposed on the external surface of theimplant body. Also preferably, the metal component in the cavity has thesame composition as the metal component on the external surface.

Optionally, the form of the metal component in the cavity is the same ordifferent compared to the form of the metal component on the externalsurface. For example, a wire or metal ribbon may be attached to themetal component on the external surface and to the cavity wall. In oneembodiment, the metal component in the cavity is in contact with aterminal of a power source disposed therein.

In a preferred option, the metal component includes a transition metaland/or a metal found in columns 10-14 of the Periodic Table of Elements,selected from gold, zinc, cobalt, nickel, platinum, palladium,manganese, and chromium. In a preferred embodiment of an inventiveimplant system, a metal component includes an antimicrobial metal whichis silver; copper; both silver and copper; both silver and cadmium; bothcopper and cadmium; or a combination of silver, copper and cadmium. Infurther embodiments, the metal component includes a metal selected fromthe group consisting of: gold, zinc, cobalt, nickel, platinum,palladium, manganese, chromium; or a combination of these.

In a further preferred option, the metal component is more electricallyconductive than the biocompatible material of the implant body.

One form of a metal component is a coating disposed on the externalsurface of the implant body. Such a metal coating ranges in thicknessbetween 1×10⁻⁹-5×10⁻³ meters, inclusive.

Optionally, a metal coating disposed on a portion of the externalsurface of the implant body covers a portion of the external surfaceranging from 1-100% of the total external surface of the implant body,excluding any portion of the external surface occupied by the insulator.Further optionally, the metal coating disposed on a portion of theexternal surface of the implant body covers a portion of the externalsurface ranging from 50-99 percent of the external surface of theimplant body. Preferred is a configuration in which the metal coating isdisposed as a single region of continuous coating on the externalsurface.

In one embodiment of an inventive medical implant system the implantbody includes an articular surface which does not include a metalcomponent such as a metal coating.

In another option, a metal component is provided in the form of a wire,ribbon, or foil disposed on the external surface.

An inventive system may be configured such that the power source iscontinuously powering a current conducted to the metal component forrelease of metal ions. Alternatively, a system includes a switch forpowering the current on or off. In a further embodiment, the current ismodulated by circuitry adapted to control the current so as to increaseor decrease the amount of current flowing and the amount of metal ionsreleased. Thus, a resistor in electrical communication with the powersource is optionally included. In a preferred embodiment, the resistorand power source are positioned in an internal cavity of the implantbody. Optionally, a switch in electrical communication with the powersource is included to control the power source. Further optionally, acontroller in signal communication with the switch is provided. Such acontroller is operated to send a signal to a system component adapted toreceive the signal and to control the switch. Preferably, a controlleris external to an individual having the implant, such that activation ofthe switch may be performed by a doctor, technician or by the patient.

Also described is a method for inhibiting microbial infection associatedwith an orthopedic implant, which includes providing an inventive systemand delivering a current to a metal component disposed on an externalsurface of an implant body, the implant body located in a human body ata site of potential infection. Delivery of current to the metalcomponent is associated with antimicrobial action such as release ofmetal ions toxic to an infectious microbe at the site of potentialinfection, such that microbial infection is inhibited.

In one embodiment of an inventive method, the infectious microbe is aGram positive bacterium and the metal component comprises anantimicrobial metal selected from the group consisting of: silver;copper; both silver and copper; both silver and cadmium; both copper andcadmium; and a combination of silver, copper and cadmium. In additionaloptions, the infectious microbe is a Gram negative bacterium and themetal component comprises an antimicrobial metal selected from the groupconsisting of copper; and both copper and cadmium. In furtherembodiments, the infectious microbe is a fungus and the metal componentcomprises an antimicrobial metal selected from the group consisting of:silver; and both silver and copper.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a line drawing of an apparatus according to an embodiment ofthe invention in the form of a hip joint implant showing a portion ofthe exterior of the implant and a cut away portion;

FIG. 1A is a line drawing of an apparatus according to an embodiment ofthe invention in the form of a hip joint implant showing an exteriorview of the implant;

FIG. 2 is a line drawing of an inventive bone screw implant system;

FIG. 3 is a schematic circuit diagram of a preferred version of animplant system according to the present invention;

FIG. 4 is a line drawing of an inventive bone screw implant systemincluding an insulator;

FIG. 4A is a line drawing of a view of an insulator;

FIG. 5 is a line drawing of an inventive hip implant system including aninsulator;

FIG. 5A is a line drawing of a view of an insulator;

FIG. 6 is a line drawing of an apparatus according to an embodiment ofthe invention in the form of a hip joint implant showing an exteriorview of the implant;

FIG. 7 is a line drawing of an apparatus according to an embodiment ofthe invention in the form of a hip joint implant showing an interiorview of the implant;

FIG. 8 is a line drawing of an external fixation device illustrated insitu;

FIG. 9 is a line drawing of an apparatus according to an embodiment ofthe invention in the form of a hip joint implant having a power sourceexternal to the body of the patient;

FIG. 10 is a line drawing of a hip joint implant apparatus according toan embodiment of the invention, showing transmission of a signal to theapparatus in situ;

FIG. 11 is a graph illustrating a “killing curve” of S. aureus; and

FIG. 12 is a graph illustrating a “killing curve” of E. coli.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods and apparatus for prevention andinhibition of implant-associated infection.

A medical implant system is provided which allows for release ofmicrobe-inhibiting metal ions in the vicinity of a temporary orpermanent surgically implanted device. In particular, metal ions arereleased from a metal component of an implant by application of anelectrical current to the metal component. A power source for producingthe electrical current is provided which may be external to the implant,or preferably, contained within the implant.

A medical implant system is provided which includes an implant body madeof a biocompatible material. A metal component is disposed on theexternal surface of the implant body and a power source is included topower delivery of an electrical current to the metal component. Theelectrical current is delivered to the metal component via an electricalconduit. In a preferred embodiment, the metal component is differentthan the biocompatible material. Thus, where the biocompatible materialis a metal, the metal component differs in composition from thebiocompatible material. For instance, preferably, the metal componenthas a higher conductivity than the biocompatible material.

Highly preferred is a medical implant system which includes an implantbody having a first element having a first external surface and a secondelement having a second external surface, as well as a first metalcomponent containing an antimicrobial metal which is disposed on atleast the first external surface of the implant body. A power sourcehaving a first terminal and a second terminal is included in aninventive implant and the first terminal is in electrical communicationwith the first metal component. The second terminal is in electricalcommunication with the second external surface. An insulator is placedin a current path between the first terminal of the power source and thesecond terminal of the power source preventing current flowing from thefirst terminal from reaching the second terminal without completing acircuit including a conductive body tissue or fluid adjacent to theexternal surface of the implant system when implanted.

In a preferred option, a second metal component containing anantimicrobial metal is disposed on the second external surface, and thesecond terminal is in electrical communication with the second metalcomponent. In such a configuration, the insulator insulates the firstmetal component from the second metal component.

The term “implant body” as used herein refers to an orthopedic implantfor replacement or repair of a component of the musculoskeletal system.For example, an orthopedic implant includes a joint replacementprosthetic implant for joint replacement or repair. Prosthetic implantsinclude those for replacement or repair of any joint illustrativelyincluding a knee, a hip, an ankle, a shoulder, a wrist, and a finger ortoe joint among others. Further, an orthopedic implant is an orthopedicfixation device used in replacement or repair of a component of themusculoskeletal system, such as a plate, wire, screw, pin, rod, nail orstaple. An orthopedic fixation device may include multiple fixators suchas a plate, wire, screw, pin, rod, nail or staple. In one preferredembodiment, an implant body is an implant body which is wholly containedwithin a patient's body when in use for the purpose of the implant.

An implant body may include two or more separate or separable elementswhich are implanted or partially implanted together, illustrativelyincluding a main implant body, a cap and two or more fixators. Thus, incertain preferred embodiments, an inventive implant system includes atleast a first element and a second element of an implant body.

In additional preferred embodiments, an implant body is partiallyexternal, for example, an external fixation device. An external fixationdevice includes one or more fixators which are partially external to thepatient's body in use. An external fixation device may further include asupport for the one or more fixators.

The term “biocompatible material” as used herein refers to a materialwhich is relatively inert in use following surgical placement into anindividual such that adverse reactions such as inflammation andrejection are rare. The biocompatible material is sufficiently strongand durable to allow the implant to perform its intended function, suchas joint replacement or fixation. Exemplary biocompatible materialsinclude metal materials such as surgical stainless steel, titanium, andtitanium alloys; ceramics; plastics; and combinations of these.

The metal component includes a metal which inhibits infection bymicrobes, such as bacteria, protozoa, viruses, and fungi. Suchantimicrobial metals include transition metals and metals in columns10-14 of the periodic table. Such metals illustratively include silver,gold, zinc, copper, cadmium, cobalt, nickel, platinum, palladium,manganese, and chromium. In certain embodiments, lead and/or mercury maybe included in amounts not significantly toxic to the patient. Highlypreferred is a metal component containing an antimicrobial metal whichgenerates metal ions in response to application of current to the metalcomponent as described herein.

A metal component contains an amount of an antimicrobial metal, theamount in the range of 1%-100% by weight of the total composition of themetal component. In general, a metal component included in an inventiveimplant system contains an amount of an antimicrobial metal in the rangeof about 1 nanogram to about 1 kilogram. A metal component preferablycontains at least 50 percent by weight of an antimicrobial metal,further preferably contains at least 75 percent by weight of anantimicrobial metal and still further preferably contains at least 95percent by weight of an antimicrobial metal. In another preferredembodiment, the metal component is substantially all antimicrobialmetal. In particular, the metal component is capable of releasing ametal ion when an electrical current is applied to the metal component.

Materials other than an antimicrobial metal may also be included in ametal component. For instance, a metal component may further includemetals which are non-antimicrobial in one configuration according to theinvention, for instance to provide structural support and lower cost ofthe metal component. In an alternative embodiment, a non-metalconstituent is included in the metal component, for instance to providestructural support and lower cost of the metal component. Exemplarynon-metal constituents include such substances as inorganic and organicpolymers, and biodegradable materials. A non-metal constituent ornon-antimicrobial metal included in a metal component is biocompatible.Preferably, the metal component is electrically conductive.

A metal component may be provided in any of various forms,illustratively including, a substantially pure metal, an alloy, acomposite, a mixture, and a metal colloid. Thus, in one embodiment, ametal component is a substance doped with an antimicrobial metal. Forinstance, in a particular example, a stainless steel and/or titaniumalloy including an antimicrobial metal may be included in a metalcomponent.

The antimicrobial properties of silver are particularlywell-characterized and a metal component preferably contains an amountof silver, the amount in the range of 1 percent-100 percent by weight ofthe total composition of the metal component. A metal componentpreferably contains at least 50 percent by weight of silver, furtherpreferably contains at least 75 percent by weight silver and stillfurther preferably contains at least 95 percent by weight silver. Inanother preferred embodiment, the metal component is substantially allsilver.

Copper is also a preferred metal included in a metal component and ametal component preferably contains an amount of copper in the range of1%-100% by weight of the total composition of the metal component. Inone embodiment, at least 50% by weight copper is included, furtherpreferably a metal component contains at least 75% by weight copper andstill further preferably contains at least 95% by weight copper. Inanother preferred embodiment, the metal component is substantially allcopper. In particular, the metal component is capable of releasing ametal ion when an electrical current is applied to the metal component.

A combination of metals is also contemplated as included in a metalcomponent. In some instances, certain metals may be more effective atinhibiting growth and/or killing particular species or types ofbacteria. For example, particular metals are more effective atinhibiting growth and/or killing Gram positive bacteria, while othermetals are more effective against Gram negative bacteria as exemplifiedin the Examples described herein.

In a particular embodiment, both silver and copper are included in ametal component. A combination of silver and copper may provide asynergistic antimicrobial effect. For instance, a lesser amount of eachindividual metal may be needed when a combination is used. Additionally,a shorter treatment time may be indicated where a synergistic effect isobserved. The ratio of copper to silver in a metal component may rangefrom 1000:1-1:1000. In one embodiment, a metal component preferablycontains an amount of a copper/silver combination in the range of 1-100percent by weight of the total composition of the metal component. Inone embodiment, at least 50 percent by weight of a copper/silvercombination is included, further preferably a metal component containsat least 75 percent by weight of a copper/silver combination and stillfurther preferably contains at least 95 percent by weight of a copperand silver in combination. In another preferred embodiment, the metalcomponent is substantially all copper and silver.

In a further preferred embodiment, a metal which has antimicrobialproperties but which does not have increased antimicrobial propertieswhen an electrical current is applied to the metal is included in ametal component. For example, cadmium has antimicrobial propertieseffective against a wide range of microbes, as described in theExamples, and which are not increased by application of an electricalcurrent. Such a metal is optionally included in a metal component alongwith one or more metals capable of releasing a metal ion when anelectrical current is applied to the metal component. In particularlypreferred embodiments, cadmium and silver, cadmium and copper, orcadmium, silver and copper are included in a metal component. The ratioof one or more metals capable of releasing a metal ion when anelectrical current is applied to the metal component to one or moremetals whose antimicrobial activity is not increased when an electricalcurrent is applied in a metal component may range from about1000:1-1:1000.

In one embodiment, a metal component preferably contains an amount of acopper and/or silver and an amount of cadmium such that the ratio ofcopper and/or silver to cadmium is in the range of about 1000:1-1:1000.A combination of silver and/or copper and cadmium in a metal componentis in an amount in the range of about 1-100 percent by weight of thetotal composition of the metal component. In one embodiment, at least 50percent by weight of a copper and/or silver and cadmium combination isincluded, further preferably a metal component contains at least 75percent by weight of a copper and/or silver and cadmium combination andstill further preferably contains at least 95 percent by weight ofcopper and/or silver and cadmium in combination. In another preferredembodiment, the metal component is substantially all copper and/orsilver and cadmium. These and other combinations of antimicrobial metalsin a metal component allow for tailoring an implant to a specifictherapeutic situation.

In a preferred embodiment, the metal component is in the form of acoating disposed on the external surface of the implant body. Thecoating can be applied by any of various methods illustrativelyincluding dunk coating, thin film deposition, vapor deposition, andelectroplating. The metal component in the form of a coating ranges inthickness between 1×10⁻⁹-5×10⁻³ meters, inclusive, preferably1×10⁻⁷-4×10⁻³ meters, inclusive, and more preferably between0.5×10⁻⁶-5×10⁻⁴ meters in thickness.

In an example including a silver coating metal component, the totalamount of silver used during the coating process ranges between about 1nanogram in weight and about 100 grams in weight. Such a coating is atleast 1 nanogram in weight in order for enough silver material to bepresent for the ionization to occur. The total weight of silvertypically does not exceed about 100 grams in order to maintain anontoxic state for the patient. However, both the lower and higher endsof this range may depend on the size and configuration of a particularimplant and the localization of the metal component in relation to theimplant body and are not intended to be limited to this range. In anembodiment including a metal coating disposed on the external surface ofthe implant body, a metal coating is preferably disposed on at least 50percent of the external surface of the implant body, and more preferablya coating is disposed on at least 75 percent of the external surface ofthe implant body. In an embodiment including a metal coating disposed onthe external surface of the implant body, the coating is optionallydisposed on substantially all of the external surface of the implantbody. In a further option, the implant body is coated with the metalcoating on substantially all of the external surface excluding one ormore articular wear surfaces. An “articular wear surface” is a portionof an implant body which is exposed to wear during normal use whenimplanted. For example, a hip joint implant includes articular wearsurfaces at the interface of the “ball” and “socket” components of thejoint prosthesis, that is, at the acetabular surfaces. Where the implantbody is a fixation device, it is preferred that the coating is presenton at least 50 percent of the external surface of the implant body, andmore preferably on at least 75 percent of the external surface of theimplant body, and further preferably on substantially all of theexternal surface of the implant body, including threads where the deviceis a bone screw.

A coating may be disposed on a surface of an implant in a patternedfashion. For example, interlocking stripes of a metal component and aninsulator may be arranged on a surface of an implant. Such a pattern ispreferably designed to inhibit microbes around the entire perimeter ofan implant. Thus, the distance between discontinuous regions of acoating is selected to account for the diffusion distance of ionsgenerated from an antibacterial coating in response to an appliedelectrical current. Typically, ions diffuse a distance in the range ofabout 1-10 millimeters.

It is appreciated that, in the context of preferred embodiments of animplant system according to the present invention including at least twoelements of an implant body, each element having a metal component,wherein the metal components are electrically isolated by an insulator,that each element optionally includes a metal component in the form of ametal-containing coating. In this context, the metal-containing coatingon the one or more elements of the implant body is preferably present onat least 50 percent of the external surface of one or both elements ofthe implant body. More preferably the metal-containing coating on theone or more elements of the implant body is preferably present on atleast 75 percent of the external surface of one or both elements of theimplant body, and further preferably the metal-containing coating on theone or more elements of the implant body is preferably present onsubstantially all of the external surface of the one or more elements ofthe implant body, including threads where the device is a bone screw.However, an insulator disposed in a current path between the metalcontaining coating on the surface of the one or more elementselectrically insulates one element from another and thus does notinclude a metal-containing coating in electrical communication with ametal-containing component on the one or more elements of the implantbody.

A metal coating on an element of an implant body is preferably disposedon the external surface as a single continuous expanse of the coatingmaterial.

Optionally, the metal component is in the form of a wire, ribbon, orfoil disposed on the external surface of an implant body. Such a metalcomponent may be attached to the implant body by welding, by anadhesive, or the like.

In another embodiment, the implant body may include an antimicrobialmetal such that the implant body or portion thereof is the metalcomponent. A second metal component may be further included in contactwith such an implant body. Thus, for example, an implant body or portionthereof may include an alloy of stainless steel and an antimicrobialmetal, and/or an alloy of titanium and an antimicrobial metal. Acommercial example of such a material is stainless steel grade 30430which includes 3% copper.

In a further embodiment, an implant body made of a material including anantimicrobial metal may be formulated such that the antimicrobial metalis distributed non-uniformly throughout the implant body. For instance,the antimicrobial metal may be localized such that a greater proportionof the antimicrobial metal is found at or near one or more surfaces ofthe implant body.

In order to deliver an electrical current to the metal component andrelease antimicrobial metal ions, a power source is included in aninventive system. A power source may be any of various power sourcessuch as a battery, capacitor, or connection to external AC. Such powersources are known in the art.

In one embodiment of an inventive system, a power source is implanted inthe body of an individual receiving a joint prosthesis. An implant powersource in such an embodiment is self-contained, that is, requiring noconnection to external power. Illustrative examples include anelectrochemical cell such as a battery and a capacitor. In a preferredembodiment, the implant body has an internal cavity housing the powersource and, optionally, other components of the system, includingcircuitry adapted to modulate a current from the power source.

An internal cavity in an implant body includes a wall defining thecavity and an opening for insertion of a power source and, optionally,other components of the system.

In general, a preferred power source housed in an implant body cavity islightweight and sized to fit in the cavity. In addition, a power sourcehoused in an implant body cavity is capable of producing electricalcurrents in the range of 0.1-200 microamps. A power source housed in animplant cavity may be selected according to the requirements of apatient. For example, a temporary implant may not require a power sourcehaving as long a life expectancy as a permanent implant.

In a further embodiment, circuitry adapted to modulate an electricalcurrent is included in an inventive system. Metal ions can be mobilizedin greater quantities by increasing the current that is applied to theimplant. If the current is increased a greater concentration of metalions, preferably silver ions, will be provided near the surface of theimplant. The greater concentration of silver ions will create a greaterdiffusion constant and provide for a greater distance of penetration bythe ions. Similarly, current may be modulated to decrease ion release asdesired, such as where no infection is believed to be present.

For example, a resistor, a switch, a signal receiver, a relay, a signaltransmitter, transformer, a sensor, or a combination of these or othersuch components and connectors may be included, optionally configured asa circuit board arrangement. In a preferred embodiment, all or part ofthe circuitry adapted to modulate an electrical current included in aninventive system is housed in a cavity in the implant body of anorthopedic implant.

Thus, optionally, the internal cavity also contains a resistor formodulation of the current. For example, a resistor in series with abattery allows use of a larger size battery with a greater lifetime. Theresistor in series can be used to reduce current flow to a desiredlevel.

Once a power source capable of producing the required current and of theappropriate size is determined, a resistance can be calculated by usingthe equation; V=I*R, where V is the voltage of the battery that has beenselected, I is the current, 1 microampere, and R is the resistance thatwill allow for the current to flow from the determined battery. Thisresistor then can be placed in series with the power source to yield therequired current. A resistor is selected with reference to otherconsiderations as well, including for example, the desired lifetime ofthe power source, the desired voltage and/or current. It is noted thatneither the current nor the voltage delivered from a power source willbe altered by the size of the implant.

In a specific example, a surface mounted chip resistor will satisfy therequirements of the resistor for use in this application. Surfacemounted chip resistors come in a variety of resistances, ranging form 1ohms up to 51 mega-ohms. Surface mounted chip resistors are manufacturedin a variety of sizes which will meet the size constraints. For example,the Ohmite, thick film high voltage SMD chip, series MMC08 will easilyfit within the shaft of the redesigned hip implant. The MMCO8 hasdimensions of over all length of 2.0 millimeters and over all width of1.25 millimeters. This particular resistor is manufactured in resistancebetween 100 ohms and 51 mega-ohms.

An inventive implant system may be configured such that a desired amountof an antimicrobial metal ion is released over a specified period oftime so as to optimize the inhibitory effects on undesirable microbesand minimize any unwanted side effects. In one embodiment, an inventiveimplant system is configured such that an included power source is incontinuous operation and metal ions are released continuously.

In a preferred option, a switch is included in an inventive system tocontrol current to flow from the power source to the metal component. Aswitch allows antimicrobial ions to be released during specified periodsof time by controlling current flow. For example, the switch is turnedon to activate current and release antimicrobial ions at regularintervals, such as once a week or once a month, for a time followingimplantation in order to prevent infection. Further, where an infectionis detected or suspected, the switch is activated to allow current flowand release of metal ions to combat the infection. An included switch iscapable of withstanding the current and the voltage transferred acrossit. It is appreciated that all components included in an inventiveimplant system are selected to withstand use and the environment when insitu over a desired period of time.

A switch is optionally and preferably controlled by a controllerexternal to the body of the individual having an implanted prosthesis.An external controller may emit a signal operative to control a switch.In one example, a magnetically controlled switch, such as a reed switchis used. Magnetically based switches that are externally controlled by acontroller are currently manufactured and are available from commercialsources. Such switches are controlled by a controller including a magnetwhich is placed in proximity to the switch in order to turn the switchon or off. For example, a magnet may be positioned in the vicinity of apatient's hip in order to activate a magnetically controlled switch inan internal cavity of a hip prosthesis implant. Thus, the switch is insignal communication with the controller.

Optionally, a transmitter is included in an inventive system which is insignal communication with receiver circuitry adapted to operate a switchand modulate current flow. Preferably the transmitter is activatedexternal to the body of an individual having an implanted prosthesis asdescribed herein. For example, a radio frequency transmitter may be usedto transmit a radio frequency signal to receiver circuitry in theinternal cavity of the implant body adapted to operate a switch andmodulate current flow.

In a further embodiment, microchip circuitry, programmed to modulatecurrent flow is included in an inventive system. Preferably, themicrochip circuitry is included in a cavity of an inventive implantbody. In a further embodiment, such microchip circuitry may be implantedat a second location in the implant patient, such as just under theskin, to remotely control the current flow.

A sensor may be included to sense microbial growth, such as bacterialgrowth, on an external surface of an implant body, or elsewhere on theimplant. Such a sensor may communicate a signal indicating bacterialgrowth to circuitry adapted to activate a switch, stimulating release ofmetal ions and inhibiting the microbes.

Preferably, the implant body having a power source in an internal cavityis adapted to be disposed totally within a human body when in use. Thus,the implant body preferably has substantially the same dimensions andshape of a conventional implant body.

In a preferred option, a portion of the metal component is disposed inthe internal cavity. For example, in a preferred option, a metal coatingis present on a portion of the wall of the internal cavity. Such a metalcoating is preferably continuous with a metal component, such as acoating, disposed on the external surface of the implant body.Optionally, and preferably, a metal component present in the internalcavity is in electrical contact with one terminal of a power sourcepresent in the cavity. A metal component present in the cavity may alsobe in the form of a wire, ribbon, or foil.

Preferably the metal component in the cavity is in the same form as themetal component present on the external surface of the implant body andis continuous therewith.

In a preferred option, a metal component disposed on the externalsurface and/or internal cavity wall is more electrically conductive thanthe biocompatible material of which the implant body is made.

The internal cavity has an opening which can be closed using a cap whichmay be attached to the implant body, such as by a hinge, or completelydetachable.

A conduit for conduction of an electrical current from the power sourceis included in an inventive system. In one embodiment, the conduit isthe biocompatible material of the implant body.

In a further embodiment, a power source is external to the body of theindividual having the implanted prosthesis and the conduit traverses theskin of the individual, connecting the metal component disposed on theimplant body with the external power source.

FIG. 1 illustrates an exemplary embodiment of an inventive apparatus 100in a partial external, partial cut away view. A drawing illustrating aprophylactic bactericidal hip implant is shown having a metal componentin the form of a metal-containing coating, such as a silver coating,depicted as stippling, on the external surface 120. An internal cavity170 is shown in cut away sectional view, shown as the stripe markedregion. This cavity allows for the internal placement of the battery,switch and resistor components. A switch 130, resistor 140 and battery150 are shown, which are contained in the cavity. Although the resistorand switch are shown in particular order with respect to the battery andcurrent path, these components may be placed elsewhere in the currentpath and in different respective order in this and other embodiments.The remaining end of the original shaft has been machined to form a cap160 so that the cap 160 is disposed so as to form a cover for cavity 170after assembly of the internal components in the cavity. In a particularembodiment, the cap forms a hermetic seal for the cavity such thatcomponents internal to the cavity are protected from the externalenvironment and, in addition, the patient's body is protected fromexposure to the components in the cavity. In this example, no coating ispresent on surfaces tending to wear due to interaction with otherimplant parts or natural elements of the body, e.g. articular surfaces,as shown without stippling or stripe marks at 180.

FIG. 1A shows an external view of a hip implant body 100 illustrating ametal coating, such as a silver coating, shown as stippling, present onan external surface 120 of the implant body. The coating is present onthe cap 160 as well in this illustration but not on articular or wearsurfaces as shown at 180.

A conduit from one terminal of the power source to a metal component isoptionally provided in the form of a wire extending there-between. Asnoted above, a further connection between the metal component and asecond terminal of the power source is optionally provided.

In a further preferred embodiment of the invention, a metal component isin removable contact with the implant. For example, a metal component inremovable contact with an implant may have the form of a metal wire incontact with an implant surface.

In another embodiment of an inventive system, a conduit is providedwhich extends outside of the body of an individual having an implantprosthesis according to the invention. For example, a conduit isprovided in the form of a wire such that one end of the wire may bepositioned in proximity to the metal component of an implantedprosthesis, preferably in contact with the metal component in order todeliver current and release metal ions from the metal component. Theopposite end of the wire optionally may extend outside the body tocontact a power source. The conduit is optionally removed when risk ofinfection is low and may be repositioned for stimulation of metal ionrelease as desired.

FIG. 2 illustrates an implant body in the form of a fixation device,particularly, a bone screw 210. An external surface 220 of the implantbody includes a metal component in the form of a continuous metalcoating, including coating on screw threads.

Also shown is a switch 230, a resistor 240 and a battery 250 inserted inan internal cavity 270 shown in the cut away region marked by stripes.Also shown is a cap 260 for closing the cavity and protecting thecomponents disposed in the cavity from the external environment, as wellas limiting exposure of cells to the components disposed in the cavity.A metal coating 280 is shown inside the cavity 270. An embodiment inwhich a metal coating is also present on the threads 290 of theillustrated bone screw is depicted in this illustration.

The configurations shown in FIGS. 1 and 2 allow for a dead endelectrical circuit between the battery and the external silver surface.Current will flow through the better conductor, the silver coating, tothe external surface and thus avoid the much poorer conductor, theinternal residual hardware device. However, it has been found thatembodiments which do not include a dead end circuit produce improvedantimicrobial effects.

In a highly preferred embodiment, an inventive medical implant systemincludes an insulator such that current flowing from a first terminal isprevented from creating a short circuit. Thus, an insulator is placed ina current path from the first terminal of a power source in order toprevent current from reaching the second terminal without completing acircuit including a conductive body tissue or fluid in the vicinity ofthe implanted implant system.

FIG. 3 illustrates a schematic circuit diagram of such a highlypreferred embodiment. A first metal component disposed in electricalconnection with a first element of an implant body is shown at 320 and asecond metal component disposed in electrical connection with a secondelement of an implant body is shown at 322. Each of the metal components320 and 322 is in electrical communication with a power source 350, thefirst metal component 320 in electrical communication with a firstterminal 312 of the power source 350 and the second metal component 322in electrical communication with a second terminal 314 of the powersource 350. Conduits 352 and 354 illustrate electrical connectorsbetween the first and second metal components 320 and 322 and the firstand second terminals 312 and 314, respectively, of the power source.Also illustrated are an optional resistor 330 and an optional switch340, each in electrical communication with the power source.

Joint replacement or repair implants include one or more implantableparts which may be included as an implant body in an inventive system.For example, a hip joint replacement implant typically includes afemoral part, replacing the natural femoral head, and a socket part, oracetabular cup or shell, replacing the natural acetabulum. While aninventive system is extensively discussed herein with regard to animplant body which is a femoral part of a hip joint replacementprosthetic implant, it is appreciated that the socket part, or cupportion of a hip implant prosthesis may also be included in an inventivesystem and configured to include an internal cavity containing a powersource and other components as described herein. A further example ofjoint replacement implant parts include a wrist implant having a carpalcomponent, for instance present where a first row of carpal bones isremoved, and a radial part, for instance inserted or attached to theradius bone. The radial part may provide an articular surface forinteraction with a carpal part. Another example is a knee jointprosthetic implant, having a femoral part attached to the femur and atibial part attached to the tibia, each having an articular surface forinteraction with the other. It is appreciated that one or more parts ofan implant prosthesis may be configured to include an internal cavitycontaining a power source and other components as described herein.Thus, an inventive system may include more than one implant body. In afurther option, each of the multiple implant bodies may include a cavityand power source, and may further include other components, preferably aresistor and switch, as described. In a further option, multipleswitches may be controlled separately, for instance where one implantbody or region in the vicinity of the implant body is more vulnerable toinfection than another, a switch in that implant body may be activatedto turn on current in that implant body without turning on current inanother implant body.

As noted, an implant may be a temporary implant, intended to remainimplanted for a limited period of time, or a permanent implant, intendedto remain implanted long-term, even as long as the remainder of theindividual's life. One type of temporary implant is known as a “spacer”implant. A spacer implant typically has a similar size and shapecompared to a permanent or short-term implant. A spacer implant istypically implanted in order to maintain the spatial integrity of anarea where a permanent joint replacement implant will be positionedeventually. For example, where an individual has a badly infectedimplant which must be removed, a spacer implant may be implanted whilethe infection is being fought.

An inventive system is particularly advantageous in such a situationsince a synergistic effect of an inventive antimicrobial system with acourse of systemic or local antibiotics is achieved. Further, aninventive spacer implant may lessen or eliminate the need for use ofbone cement, currently used in this situation. The insertion of a spacerimplant would allow the patient to be much more active than if the jointwere filled with bone cement. Further, tissue encroachment at the siteis decreased by placement of a spacer implant.

In one embodiment, a power source, such as a battery, having a firstterminal, a second terminal, and a potential difference between thefirst and second terminals, is provided. Further provided is a conduitfor an electrical connection between the first terminal and the metalcomponent. Also provided is a conduit for an electrical connectionbetween the metal component and the second terminal.

In a preferred embodiment, an electrical circuit is completed betweenthe metal component and the second terminal through a tissue or fluid ofa body in which an inventive system is implanted.

As noted above, in a highly preferred embodiment, an inventive medicalimplant system includes an insulator such that current flowing from afirst terminal is prevented from creating a short circuit. Thus, aninsulator is placed in a current path from the first terminal of a powersource in order to prevent current from reaching the second terminalwithout completing a circuit including a conductive body tissue or fluidin the vicinity of the implanted implant system.

In a particular example, referring to FIG. 4, an implant body is shownin the form of a fixation device, particularly, a bone screw 400. Anexternal surface 420 of the implant body includes a metal component inthe form of a continuous metal coating, including coating on screwthreads. Also shown is a switch 430, a resistor 440 and a battery 450inserted in an internal cavity 470. The battery has a first terminal 412and a second terminal 414. Also shown is a cap 460 for closing thecavity and protecting the components disposed in the cavity from theexternal environment, such as body tissue or fluids 422, as well aslimiting exposure of cells to the components disposed in the cavity.Further shown is an insulator 485. In this example, a current path isestablished from the first terminal 412 of the battery 450 through theimplant body 410 which serves as a conduit for current to a metalcomponent 420, and continuing through the body tissue or fluids 422 inwhich the implant is located and through the cap 460 to the secondterminal 414 of the battery 450. The insulator 485 prevents shortcircuiting of the current, for instance through the implant body to thesecond terminal of the battery 414. FIG. 4A shows insulator 485 viewedalong broken line 498 shown in FIG. 4. The insulator 485 shown in FIG.4A includes a conductive portion 487 configured such that current canpass through to the second terminal 414. Such a conductive portion maybe a portion made of a conductive material. In another option, aconductive portion may be an opening through a non-conductive region ofthe insulator.

In another particular example, FIG. 5 illustrates an implant body in theform of a hip implant 500. An external surface 520 of the implant bodyincludes a metal component 520 in the form of a continuous metalcoating. Also shown is a switch 530, a resistor 540 and a battery 550inserted in an internal cavity 570. The battery has a first terminal 512and a second terminal 514. Also shown is a cap 560 for closing thecavity and protecting the components disposed in the cavity from theexternal environment, such as body tissue or fluids 522, as well aslimiting exposure of cells to the components disposed in the cavity.Further shown is an insulator 585. In this example, a current path isestablished from the first terminal 512 of the battery 550 through theimplant body 510 which serves as a conduit for current to a metalcomponent 520, and continuing through the body tissue or fluids 522 inwhich the implant is located and through the cap 560 to the secondterminal 514 of the battery 550. The insulator 585 prevents shortcircuiting of the current, for instance through the implant body to thesecond terminal of the battery 514. FIG. 5A shows insulator 585 viewedalong broken line 598 shown in FIG. 5. The insulator 585 shown in FIG.6A includes a conductive portion 587 configured such that current canpass through to the second terminal 514. Such a conductive portion maybe a portion made of a conductive material. In another option, aconductive portion may be an opening through a non-conductive region ofthe insulator.

Optionally, an insulator is configured to provide a threaded fit into aninternal cavity, thus insulating a cap from the walls of the cavity andthereby insulating the cap from the implant body. For example, aninsulator in the form of a threaded insert such as a Helicoil, isprovided for threaded engagement with a wall of an internal cavity andnon-threaded engagement with the wall of a cap.

An insulator may be made of any non-electrically conductive material.Optionally, an insulator is made of a biocompatible material. Suitablematerials include ceramics, plastics and other polymers, such as rubber.An insulator may be provided in any of various forms in order to preventshort circuiting in an inventive implant system. For example, aninsulator may be a body of a non-electrically conductive materialdisposed in the current path between the first terminal of the powersource and the second terminal of the power source preventing currentflowing from the first terminal from reaching the second terminalwithout completing a circuit including a conductive body tissue or fluidadjacent to the external surface of the implant system when implanted ina patient body. Further, an insulator may be a coating of anon-conductive material disposed in the current path.

FIG. 6 illustrates an apparatus 600 according to an embodiment of theinvention in the form of a hip joint implant showing an exterior view ofthe implant. A hip implant is shown having a metal-containing coating620, depicted as stippling, on the external surface. Three sections ofthe hip implant are shown, a main body 630, an intermediate insulatorsection 640 and a cap 660. The insulator section 640 electricallyinsulates the first metal component, the antimicrobial metal-containingcoating on the main body 630 from the second metal component, theantimicrobial metal-containing coating on the cap portion 660. In theillustrated embodiment, the surface 622 and body of the intermediatesection 640 is an insulator in the current path between the first andsecond terminals of a power source. An internal cavity 670 is indicated.This cavity allows for the internal placement of the battery, switch andresistor components. In this embodiment, main body 630 and the cap 660each include a male connector 680 for secure attachment of the main body630 to the intermediate insulator section 640 and for secure attachmentof the cap 660 to the intermediate insulator section 640. As depicted,the male connectors 680 are threaded for reciprocal engagement with athreaded portion of the intermediate insulator section 640. Any type ofconnector may be used however, illustratively including “snap” fittingof the components. Assembly of the main body 630, intermediate insulatorsection 640 and cap 660 forms a hermetic seal for the cavity such thatcomponents internal to the cavity are protected from the externalenvironment and the patient's body is protected from exposure to thecomponents in the cavity. No metal component is present on surfacestending to wear due to interaction with other implant parts or naturalelements of the body as shown by sections without stippling at 690.

FIG. 7 illustrates an interior view of a portion of an implant such asshown in FIG. 6. The three sections of the hip implant described in FIG.6, a main body 630, an intermediate insulator section 640 and a cap 660are shown in section, along with male connectors 680 in reciprocalengagement with a threaded portion of the intermediate insulator segment640. An internal cavity 670 is also shown. Shown in the internal cavity670 are a switch 612, a resistor 614, and a power source in the form ofa battery 618. In the illustrated embodiment, a metal component 620 inthe form of a metal-containing coating is present on the surface of themain body 630 and a metal component 621 in the form of ametal-containing coating is present on the surface of the cap 660. Themetal component 620 is in electrical communication with power sourceterminal 623 and the metal component 621 is in electrical communicationwith power source terminal 624. The intermediate insulating section 640insulates the main body portion 630 from the cap 660, preventing currentflowing from the first terminal from reaching the second terminalwithout completing a circuit including a conductive body tissue or fluidadjacent to the external surface of the implant system when implanted.

FIG. 8 illustrates an implant system according to the present inventionin the form of an external fixation device 800. Depicted is a firstelement in the form of a fixation rod 830, electrically connected to afirst terminal of power source 818 by a conduit 842. A second element840 is electrically connected to a second terminal of the power source818 by a conduit 844. A structural support 850 for fixation rods 830 and840 is illustrated. Fixation rods 830 and 840 are electrically isolatedfrom each other. In particular, support 850 includes a non-conductivematerial such that current does not pass from a fixation rod through thesupport 850 to a second fixation rod.

FIG. 9 illustrates an inventive system 900 in the context of a humanbody including an external power supply 950 and a conduit 970 contactingan implant body 910 having a metal coating, shown as stippling, on aportion of the surface of the implant body 910. It will be noted that nocoating is present on an acetabular wear surface of the implantprosthesis. Further shown is the “cup” portion 980 of a hip replacementimplant, marked by stripes. A lead 960 is shown electrically connectingthese two portions of a hip implant. Alternatively, an insulator may bedisposed at another location in the current path, such as between twoportions of the implant body 910, for instance as shown in FIG. 5. In afurther alternative embodiment, power supply 950 may be implanted.

Another embodiment of an inventive apparatus is shown in FIG. 10 whichshows an inventive system 1000 including a hip replacement prosthesis1010 in the context of a human body. Also shown is an externalcontrolling device 1090 which may be used to modulate current flow in animplanted prosthesis by acting on internal circuitry 1080 in order tomodulate delivery of metal ions to inhibit microbes. In a preferredembodiment of such a system, an insulator is positioned in the currentpath between two components of the implant.

A method for inhibiting microbial infection associated with anorthopedic implant is provided which includes providing an inventivesystem as described and delivering a current to a metal componentdisposed on an external surface of an implant body, the implant bodylocated in a human body at a site of potential infection.

In one embodiment, an inventive method for inhibiting an infectiousorganism includes introducing an electrical current into a metalcomponent of an implanted joint prosthesis to release metal ions fromthe component. The metal ions have a biostatic or biocidal effect onmicroorganisms such that growth and/or attachment of microorganisms onthe implant and in the vicinity of the implant are inhibited. A methodaccording to the present invention is a method of treating osteomyelitisassociated with an implant in one preferred embodiment.

As noted above, biocidal metals and ions include transition metals andions. Preferred metals and ions include silver, copper, cadmium andcombinations thereof. Further, metals and ions such as cobalt, nickel,platinum, gold, zinc, palladium, manganese, chromium, and othertransition metals and/or Periodic Table column 10-14 metals may beincluded.

In one embodiment, a method of inhibiting a microbial infection isprovided which includes providing an inventive implant system anddelivering a current to a silver-containing metal component disposed onan external surface of an implant body, the implant body located in ahuman body at a site of potential infection. In particular, such amethod is applicable to inhibit infections by Gram negative bacteria,Gram positive bacteria, and fungus which are associated with implants.Such microbes illustratively include such bacteria illustrativelyinclude Esherichia coli, S. aureus, Pseudomonas aeruginosa, Enterococcusfaecalis, Methicillin resistant S. aureus (MRSA) and Candida albicans.

In a further embodiment, a method of inhibiting a microbial infection isprovided which includes providing an inventive implant system anddelivering a current to a copper-containing metal component disposed onan external surface of an implant body, the implant body located in ahuman body at a site of potential infection. In particular, such amethod is applicable to inhibit infections by Gram positive bacteriawhich are associated with implants. Such bacteria illustratively includeS. aureus, Enterococcus faecalis, and Methicillin resistant S. aureus(MRSA).

In another embodiment, a method of inhibiting a microbial infection isprovided which includes providing an inventive implant system anddelivering a current to a copper and cadmium and/or silver and cadmiumcontaining metal component disposed on an external surface of an implantbody, the implant body located in a human body at a site of potentialinfection.

Infectious organisms inhibited by such metals and metal ionsillustratively include bacteria, mycobacteria, viruses and fungi.Methods and apparatus according to the present invention areparticularly useful in cases involving antibiotic resistant organisms.

Generally, such metal ions inhibit infection at concentrations rangingbetween 1×10⁻³ M-1×10⁻⁷ M, inclusive, and is preferably delivered inamounts sufficient to achieve a concentration in this range. Optionally,and preferably, metal ions are delivered in amounts sufficient toachieve a concentration in the range between 5×0.25×10⁻⁶ M, inclusive.In particular, silver ions are delivered in amounts sufficient toachieve a concentration in the range between 5×10⁻⁵ M-0.25×10⁻⁶ M,inclusive.

A metal ion is released from a metal component by application of anelectrical current to the metal component. Bone and soft tissue cellsare affected by electrical current and thus the amount of currentdelivered and the length of time for which it is delivered must beconsidered in the context of the proximity of the implant to such cells.The amount of a metal ion released is dependant on the strength andduration of the electrical stimulus which is adjusted accordingly.

Generally, a current in the range of 0.1 microamps to 200 milliamps isdelivered to a metal component. In general, a current is delivered to ametal component for periods of time ranging from about 1 minute tocontinuous delivery over the lifetime of the power source, that is,weeks, months or years. In general weaker currents are used forlonger-term treatments. Thus, in a preferred embodiment, 0.3-1.5micro-amperes of current is delivered in order to ionize a silversurface layer. Also preferred is an embodiment in which 0.8-1.2microamps of current is delivered to a silver coating.

Small electrical currents in the ranges described are sufficient toionize a solid silver coating, producing silver ions. Without wishing tobe bound by theoretical considerations, according to Faraday's law,under ideal conditions 4 micrograms of silver will be liberated per hourper micro ampere of current applied to silver. Calculation 1 belowdetails this.

$\begin{matrix}{{\left( {1\; \mu \mspace{20mu} {AMP}} \right)*\left( \frac{1\mspace{14mu} {Coulomb}}{1\mspace{14mu} {Amps}*{Sec}} \right)*\left( \frac{1\mspace{20mu} {Faraday}}{96\text{,}487\mspace{20mu} {Coulombs}} \right)*\left( \frac{107.868\mspace{14mu} {{gram}{AG}}}{1\mspace{20mu} {Fraday}} \right)*\left( \frac{1*10^{6}{\mu g}}{1\; g} \right)*\left( \frac{3600\mspace{14mu} {Sec}}{Hour} \right)} = {4.02\mspace{14mu} \mu \; g\text{/}{hour}}} & \left( {{Equation}\mspace{14mu} 1.0} \right)\end{matrix}$

Assuming the power source is capable of producing a 1 micro-amperecurrent and that the electrical current should not exceed 20micro-amperes at any time, 10 micrograms/milliliter concentration ofsilver ions within a couple of hours. Additionally the maintenance of a10 micrograms/milliliter concentration of silver ions is possible withvery small electrical current requirements.

Additional theoretical considerations indicate that total lifetimeexposure to silver ions advantageously do not exceed 8.95 grams for aperson of average size, approximately 70 kilograms, and having anaverage life expectancy, about 70 years. This calculation is based onthe assumption that about 0.35 milligrams of silver can be safelyconsumed each day, see Newman, J. R., Tuck Silver 100 Safety Report,Jan. 9, 1999. Thus, for a permanent implant, it is desirable that aninventive system not contain more than about this amount of silver.Similar calculations may be made for other metal ions as will berecognized by one of skill in the art. For example, such a calculationindicates that 2.37 micrograms per hour of copper per micro ampere ofcurrent applied.

In one embodiment, a method of inhibiting bacterial infection associatedwith an implant includes administration of a systemic or localantibiotic and administration of a metal antibiotic via an inventiveimplant. A synergistic effect of such treatment is achieved as a lowerdosage of both the systemic or local antibiotic and the metal antibioticis necessary to achieve a therapeutic effect.

While inventive methods, implants and implant systems are generallydescribed with reference to use in humans herein, the methods andapparatus are also used in other animals to inhibit infection. Forexample, an inventive apparatus and method is used in animalsillustratively including cats, dogs, cattle, horses, sheep, goats, rats,and mice.

The apparatus and methods described herein are presently representativeof preferred embodiments, exemplary, and not intended as limitations onthe scope of the invention. Changes therein and other uses will occur tothose skilled in the art. Such changes and other uses are encompassedwithin the spirit of the invention as defined by the scope of theclaims.

Example 1

One embodiment of an implant body is manufactured by obtaining a hipreplacement prosthesis similar to a DePuy AML Hip System designed toinclude an internal cavity, about 10 millimeters in length and about 5millimeters in width and a cap to close the opening of the cavity asdescribed herein. Articular surfaces of the implant body are masked andthe remaining external surfaces are coated with a silver metal filmabout 1 micron in thickness. A battery, resistor and switch are chosento fit in the cavity. A portion of the cavity wall adjacent to theexternal surface of the implant body is also coated with silver metal toa depth adjacent the positive terminal of the battery. An insulator ispositioned such that short-circuiting is avoided.

A battery with the desired profile is currently in production by manybattery manufacturers. The Energizer battery number 337 satisfies all ofthe required size characteristics needed for implementation within abactericidal hip implant. When examining the Energizer 337 battery onecan see that the small size, 1.65 mm in height by 4.8 mm in diameterallow the battery to easily fit within the 5 mm compartment.

The 337 size battery provides a voltage of 1.55 volts, which is muchgreater than required for the application of ionizing a solid silvercoating. Thus, a resistor is chosen to be placed in series with thebattery. Using a voltage of 1.55 volts and a required current of 1micro-ampere one can calculate the required resistor as shown inEquations 2.1 and 2.2 below.

$\begin{matrix}{V = {IR}} & \left( {{Equation}\mspace{14mu} 2.0} \right) \\\begin{matrix}{R = \frac{V}{I}} \\{= \frac{1.55\mspace{14mu} {volt}}{1*10^{- 6}\mspace{14mu} {amperes}}} \\{= {15\text{,}550\text{,}000\mspace{14mu} {ohms}}}\end{matrix} & \left( {{Equation}\mspace{14mu} 2.1} \right)\end{matrix}$

The required resistor should have a resistance of approximately 15.5mega-ohms. Additionally the resistor must conform to the sizerequirements as set by the diameter of the pocket within the shaft ofthe implant, 5 millimeters.

Utilizing a resistor with the required 15.5 mega-ohms rating in serieswith the 337 battery will provide for approximately 75573 hours of runtime. The calculation of the run time for the battery under with thisresistance is show in calculation #3 below. During this running time thebattery will be producing the required 1 micro-ampere current that isrequired to ionize the solid silver coating.

$\begin{matrix}{\frac{{run\_ Time}({New\_ hip})}{{{MMCO}\; 8} - {Resistance}} = \frac{{run\_ Time}\left( {simulated\_ application} \right.}{{simulated} - {resistance}}} & {{Equation}\mspace{14mu} (3.0)} \\{\frac{{run\_ Time}({New\_ hip})}{15\text{,}550\text{,}000\mspace{14mu} \Omega} = \frac{486{\_ hours}}{100\text{,}000\mspace{14mu} \Omega}} & \left. {{Equation}\mspace{14mu} 3.1} \right) \\{{{run\_ Time}({New\_ hip})} = {75573{\_ hours}}} & {{Equation}\mspace{14mu} (3.2)}\end{matrix}$

An included switch, like all other components, fits within the 5millimeter diameter cavity that has been machined within the shaft ofthe original hip implant.

Additionally the switch will have the ability to be turned ON and OFFonce implanted within the human body. In this example, a magneticallybased switch is selected. Coto Technology manufactures a switch, RI-80Series Dry Reed Switch that is designed specifically for medicalapplications and which meets the design size constraints. The switch hasa maximum dimension of the central tube of 5 millimeters in length and1.8 millimeters in diameter. This switch will carry a maximum current of0.5 amperes and a has a maximum operating voltage of 200 volts, both ofwhich are satisfactory operating characteristics needed for abactericidal hip implant according to the invention.

Example 2

Procedures to identify an antimicrobial metal composition may include anexamination of each metal's antimicrobial potential using a panel ofcommon Gram (+) and Gram (−) bacterial, fungal species or othermicrobes. a method adapted from the Kirby Bauer agar gel diffusiontechnique, the antimicrobial efficacy of eight metals: silver, copper,titanium, gold, cadmium, nickel, zinc and stainless steel AISI 316L andtheir electrically generated ionic forms are tested against 5 bacterialspecies and one fungus commonly associated with osteomyelitis.

Strains of Esherichia coli, S. aureus, Pseudomonas aeruginosa,Enterococcus faecalis, Methicillin resistant S. aureus (MRSA), andCandida albicans isolated from samples submitted to the PennsylvaniaState University Animal Diagnostic Laboratory (E. coli, S. aureus, P.aeruginosa and E. faecalis) or J. C. Blair Hospital, Huntingdon, Pa.(MRSA and C. albicans), are diluted to a 0.5 MacFarland standard andinoculated onto Mueller-Hinton agar plates (Remel, Lenexa, Kans.).

Metallic wires served as the ion source, specifically: silver (99.97%purity), copper (99.95+% purity), titanium (99.8% purity), gold (99.99%purity), cadmium (99.999% purity), nickel (99.98% purity), zinc (99.999%purity) and stainless steel AISI 316L. All wires are of uniform equaldiameter (1.0 mm).

Small holes are burned into opposite sides of the Petri plates whichallowed for the aseptic threading of 32 mm lengths of test wire into theagar. Once embedded, 1 cm² of wire surface area is exposed to thegrowing microbes.

Electrical currents are generated by placing a standard 1.55 Volt AAbattery in series with one of the following resistors: 3.01 MΩ, 1.5 MΩ,150 kΩ, and 7 kΩ. A 70 mm length of each of the test metals is connectedin series with the given resistor. The current that is generated by eachof the four different resistors (3.01 MΩ, 1.5 MΩ, 150 kΩ, and 75 kΩ) is0.5 μA, 1.0 μA, 10 μA, and 20 μA respectively. The 20 μA/cm² surfacearea charge is proven in 1974 to be a safe electrical exposure value forthe cells. (Banneo 1974) As calculated with Faraday's equation, a 20μA/cm² surface area charge density produced over 80 μg/hour of silverions.

The circuit is completed by aseptically threading the anode through theopposite hole and embedding it into the agar. One control plate for eachmicrobial species is aseptically threaded with wires, but received noelectrical current. The plates are incubated in ambient air at 37° C.for 24 hours, and subsequently examined for bacterial growth and/orzones of inhibition.

Of the eight metals and metal ions tested, silver ions and cadmium showbactericidal efficacy against all bacterial species tested, and copperions showed bactericidal efficacy against Gram-positive bacteria.Titanium, gold, nickel, zinc and stainless steel AISI had no significanteffects in this example.

Exemplary results are shown in Table 1 in which numbers representmeasurements of the diameter of the zone of inhibition in millimetersaround the central wire. The table shows that silver has somemicrobicidal properties when not electrically ionized, since E. coli isinhibited by non-charged silver. A smaller current produced resultssimilar to larger currents, and in all cases the addition of currentincreased the size of the inhibition zone.

Copper also shows antimicrobial properties, both in the ionic form andthe uncharged metallic form, as summarized in Table 1. In the unchargedform copper showed bactericidal properties against E. faecalis. Aminimal current produced bactericidal results for all Gram (+) speciesof bacteria, and higher currents produced larger zones. Copper did nothave an effect on Gram (−) bacterial species at currents used.

Surprisingly, cadmium results are unique in producing antimicrobialeffects against all organisms tested, and the pattern of efficiency heldtrue both in the absence and presence of electrical stimulation.Increasing the current resulted in minimal changes in microbialresponse. Cadmium produced a double zone of inhibition: an inner zone ofcomplete clearing closer to the wire, and an outer zone of decreasedbacterial growth (incomplete clearing). For descriptive purposes, theinner zone is considered to be “microbicidal”, while the outer zone isconsidered “microbistatic”, or inhibitory. Numbers shown in Table 1reflect this double zone of inhibition such that the size of the “innerzone” is present first and the size of the “outer zone” is presented inparentheses. Additionally, cadmium consistently showed some inhibitoryeffect in the absence of electrical charge; increasing the current hadlittle additional effect.

TABLE 1 Gram Positive Gram Negative Fungus S. E. E. P. C. Current aureusfaecalis MRSA coli aeruginosa albicans Silver  0 uA 6 0 0 5 0 0 0.5 uA 18 17 18 20 18  34  1 uA 20 19 18 21 21  30 10 uA 20 21 18 25 21  32 20uA 20 20 18 24 20  30 Gold  0 uA 3 0 0 0 0 0 0.5 uA  0 0 0 0 0 0  1 uA 00 0 10 0 0 10 uA 0 0 0 0 0 0 20 uA 0 0 0 0 0 0 Titanium  0 uA 0 0 0 0 00 0.5 uA  0 0 0 0 0 0  1 uA 0 0 0 0 0 0 10 uA 0 0 0 0 0 0 20 uA 0 0 0 00 0 Copper  0 uA 0 11 0 0 0 0 0.5 uA  14 16 7 0 0 0  1 uA 6 16 6 0 0 010 uA 0 15 9 0 0 0 20 uA 8 18 11 0 0 0 Stainless steel  0 uA 0 0 0 0 0 00.5 uA  0 0 0 0 0 0  1 uA 0 0 0 0 0 0 10 uA 0 0 0 0 0 0 20 uA 0 0 0 0 00 Cadmium  0 uA 8(15) 5 14 6(18) (17)  28 0.5 uA  6(10) 6 13 5(18) (12) 28  1 uA 8(15) 6 13 4(18) (18)  31 10 uA 6(14) 5 15 6(18) (16)  30 20 uA7(15) 5 16 5(17) (18)  30 Zinc  0 uA 0 0 0 0 0 0 0.5 uA  0 0 0 0 0 0  1uA 0 0 0 0 0 0 10 uA 0 0 0 0 0 0 20 uA 0 0 0 0 0 0 Nickel  0 uA 0 0 0 00 0 0.5 uA  0 0 0 0 0 0  1 uA 0 0 0 0 0 0 10 uA 0 0 0 0 0 0 20 uA 0 0 00 0 0

Example 3 Characterization of Effective Antimicrobial Metals

A “killing curve analysis” may be performed in order to characterizeparameters which achieve an antimicrobial effect. A predetermined numberof colony forming units/ml (CFU/ml), established in a growth medium, aretransferred to a saline solution and then exposed to the antimicrobialmetal or metal form. At predetermined time intervals, an aliquot isremoved, diluted (if necessary), inoculated onto blood agar plates andincubated overnight at 37° C. The resulting growth is quantified asCFU/ml. A graph, with time as the X-axis and CFU/ml as the Y-axisdemonstrates the point at which the antimicrobial effect and microbialpopulation growth intersect. The concentration of metal required forantimicrobial effect can be determined by examining the time point atwhich the microbial population begins to decrease.

To examine the rate of diffusion of ions away from the metal source,i.e. the rate at which the microbes are inhibited from growing (orkilled), high performance microscopy may be used. A high performancemicroscopic system developed by Cytoviva allows for real-timeobservation of living cells and cellular components without the use ofstaining agents. By observing the microbial response to a given metal, a“velocity” of microbial destruction can be directly observed. The rateof diffusion of ions through agar can be inferred from the velocity ofkill.

In this example, silver is tested with respect to two differentbacterial species, E. coli and S. aureus. A current of 0.5 uA is used inthis example.

Strains of E. coli and S. aureus isolated from samples submitted to thePennsylvania State University Animal Diagnostic Laboratory, areseparately diluted to a 0.5 MacFarland standard and added to individualtest tubes containing 10 mls of sterile Tryptic Soy Broth (TSB). Asilver wire (99.97% purity) having a uniform diameter of 1.0 mm servedas a source of ions.

Two small holes are burned into the screw cap of each test tube. SilverWires (99.97% purity), having uniform diameters of 1.0 mm, served as ionsources. The wires are aseptically threaded through the screw cap holesand positioned to expose a total length of 32 mm into the previouslyinoculated TSB. This resulted in the exposure lo 1 cm² of silver wire togrowing bacterial cells. Electrical current is generated by placing astandard 1.55 Volt AA battery in series with a 3.01 MΩ resistor. Thecurrent that is generated by the 3.01 MΩ resistor is 0.5 μA whencombined into the circuit. Additionally a circuit, formed without anyresistor is utilized and inserted into a tube in an identical fashion.The circuits are completed by aseptically threading the anode throughanother hole in the test tube screw cap and into the TSB. One tube ofeach bacterial species, served as the control. It contained a silverwire, but no external circuit is connected. The silver wire as well asthe anode wire is placed in contact with the bacterially laden brothcontinued within the test tube. This setup is used to produce “killingcurves”. The tubes are incubated in air at room temperature for a totalof 8 hours. Every hour the test tube is vortexed for approximately 10seconds. The test tube cap is then opened and a 10 μl sample of broth isaseptically drawn from the test tube. The test tube are again closed andvortexed. The sample is plated onto blood agar plates using a spiralplating technique. The blood agar plates are incubated at roomtemperature for 24 hours. The number of colonies present on the bloodagar plates at 24 hours are counted and recorded.

The results clearly demonstrate that the charged form of the silvermetal has a much greater kill rate when compared to the non-chargedmaterial. A “killing curve” shown in FIG. 9 shows the killing rateassociated with S. aureus. The results clearly demonstrate a bacterialreduction rate of approximately 5.698*10E12 bacteria per hour. Withinthis time frame both the control and the silver with no resistor allowbacterial growth.

A “killing curve” for Escherichia coli in FIG. 10 shows the killing rateassociated with E. coli. The 3 MΩ resistor utilized in this circuitcorresponds to the smallest current 0.5 uA. The curve shows bacterialreduction from 320*10E6 to zero within five hours, a rate ofapproximately 72*10E6 bacteria per hour. Within this time period boththe control and the silver with no resistor tests continue to supportbacterial growth.

Example 4 Optimization of Critical Operational Parameters ofAntimicrobial Metals

Antimicrobial properties of specific metals or metal forms differ whenmodifications are made in the experimental parameters. Using data fromthe “killing curve analyses”, critical parameters will be establishedfor the generation of optimal antimicrobial effects, and can then bebalanced against the characteristics of the application into which themetal will be incorporated.

In order to evaluate any possible toxicity of antimicrobial metalcompositions on mammalian cells, in vitro cell culture systems may beutilized Specifically, batteries and resistors connected in series witha predetermined antimicrobial metal composition is aseptically threadedinto a mammalian cell culture flask and allowed to run, generating metalions within the culture. Cells are monitored during testing formorphological changes and percentages of live vs. dead cells. Inaddition, treated and control cells may be evaluated via metabolicfunction assays such as albumin and urea levels in hepatocytes; bonealkaline phosphatase levels in osteoblasts; and matrix protein levels inchrondrocytes.

In addition, the effects of circuit polarity, operation time and dutycycle are evaluated on cells in vitro using device parameters andoptimized for maximal antimicrobial effect and low toxicity. An externalcircuit is constructed allowing for varying run-time cycles andalternating circuit polarities. The external circuit with battery,resistor, an inverter for reversing polarity, and a timer will beconnected in series with the test antimicrobial metal. The circuit willbe aseptically threaded into the cell culture flask and allowed to run,generating antimicrobial ions within the culture. The continuous runningtime of the circuit as well as the polarity of the circuit will bemanipulated by varying the circuit timer and changing the polarity ofthe circuit via the switch.

Example 5 In vivo evaluation

A rat model for evaluation of the effect of an inventive deviceimplant-related osteomyelitis is described in this example. The modeluses a bacterial inoculate to promote infection, as described in Luckeet al. 2003 [please provide this reference]. S. aureus subspecies aureusRosenbach (ATCC #49230), isolated from a patient with chronicosteomyelitis, and shown to cause bone infections in rats (Solberg 1999)is utilized in this procedure as a model Gram positive organism. Thepreviously tested clinical E. coli isolate serves as the model Gramnegative organism.

Aliquots (100 microliters) of S. aureus or E. coli grown overnight intryptic soy broth (TSB) are transferred to tubes containing 3 ml ofsterile TSB. These cultures are grown to log-phase growth.Colony-forming units (CFU) per ml are confirmed by several plate countsusing a spiral plating technique. Suspensions in sterile phosphatebuffered saline (PBS) are held at −80° C. until the day of surgery. Toquantify possible loss of viable bacteria following the freeze-thawcycle, CFU/ml is confirmed after each cycle of defrosting.

Surgery is performed under general anesthesia by intraperitonealinjection of xylazine 2% (Medistar®, 12 mg/kg body weight) andketaminehydrochloride (Ketavet, 100 mg/ml; 80 mg/kg body weight). Ratsare maintained on inhaled isoflourane.

Animals are prepared for surgery as follows: One leg is shaved andscrubbed with betadine alcohol prep. To prevent accidental bacterialcontamination during surgery animals are placed on sterile drapes.Bodies are covered with sterile sheets; the prepped leg is separatelydraped in a sterile manner. A small incision (5 mm) of skin and fasciaat the proximal tibial metaphysis provides access to the tibialperiosteum. The medullary cavity of the proximal metaphysis is accessedthrough cortical and cancellous bone via al mm diameter titanium burr,leaving the surrounding periosteum intact. A steel Kirschner wire, 1.0mm in diameter, is inserted into the medullary cavity and pushed forwarddistally for smooth dilatation of the cavity for a length ofapproximately 32 mm distally, and removed. A 50 microliter microsyringeis inserted into the medullary cavity and used to inject either 10microliters of sterile PBS, or, PBS containing S. aureus or E. coli in aconcentration of 10³ CFU/10 microliter. Following inoculation, a 32 mmlength of antimicrobial test wire, representing an engineered implant(99.7% purity), or a titanium wire (99.8% purity) representing currentimplant material, is inserted into the cavity. The protruding portion ofthe test wire will attach to an external wire making the batteryconnection complete. The battery, within a battery pack will placed in arodent jacket fitted to the rat. Within the experimental groups the twogroups designated as Ag wire and electric will be identical except forthe current that is running through the implant. The delay turn on AGwire and electric group will have the wire implanted and then wait threedays before the battery is inserted into the circuit. This delay willallow for full growth of the bacterial inoculums within the rat.

All implants are performed the soft tissue will be irrigated withbetadine solution. Skin and fascia are sutured in a single knot. Allgroups designated as having an electrical current will have a batteryinserted into the circuit and the current through the circuit turned on.

Animals are sacrificed at one week, two weeks and four weeks.Post-sacrifice the implants are removed, and the tibia into which theimplant is placed is examined for gross infection. Samples are takenfrom the medullary cavity for culture and histological examination.

To assess development and progression of bone infection radiographs aretaken in posterior-anterior and lateral views on Days 0 (OP), 7, 14, 21,and 28. Proximal epi-/metaphysis, diaphysis, and distal epi-/metaphysisare examined for evaluation of infection extent and effect of implant.

Example 6

A hip implant having silver disposed on the outer surface according tothe present invention is activated to produce silver ions. The activatedimplant is implanted in agar inoculated with Grain negative bacteria, E.coli. This preparation is placed at 37° C. and observed at various timesfollowing inoculation. A “killing zone” is observed around the implant.Similar experiments with Gram positive bacteria and fungus also resultin an observed killing zone.

Example 7

A hip implant having copper disposed on the outer surface according tothe present invention is activated to produce copper ions. The activatedimplant is implanted in agar inoculated with Gram positive bacteria,MRSA. This preparation is placed at 37° C. and observed at various timesfollowing inoculation. A “killing zone” is observed around the implant.

Example 8

A hip implant having copper and silver disposed on the outer surfaceaccording to the present invention is activated to produce copper andsilver ions. The activated implant is implanted in agar inoculated withboth Gram negative and Gram positive bacteria, E. coli and MRSA. Thispreparation is placed at 37° C. and observed at various times followinginoculation. A “killing zone” for both Gram positive and Gram negativeorganisms is observed around the implant. In similar experiments, afungus, Candida albicans is used to inoculate the medium and is alsoinhibited by the activated implant.

Example 9

A hip implant having cadmium, copper and silver disposed on the outersurface according to the present invention is activated to producecopper and silver ions. The activated implant is implanted in agarinoculated with multiple microbial organisms including Gram negative andGram positive bacteria, E. coli and MRSA, as well as Candida Albicans.This preparation is placed at 37° C. and observed at various timesfollowing inoculation. A “killing zone” for all organisms is observedaround the implant.

Any patents or publications mentioned in this specification areincorporated herein by reference to the same extent as if eachindividual publication is specifically and individually indicated to beincorporated by reference.

Patents, patent applications, or publications mentioned in thisspecification are incorporated herein by reference to the same extent asif each individual document was specifically and individually indicatedto be incorporated by reference. In particular, U.S. patent applicationSer. No. 11/172,138, filed Jun. 30, 2005 and U.S. Provisional PatentApplication Ser. No. 60/708,320, filed Aug. 15, 2005, the entire contentof each of which is incorporated herein by reference.

The compositions, methods and apparatus described herein are presentlyrepresentative of preferred embodiments, exemplary, and not intended aslimitations on the scope of the invention. Changes therein and otheruses will occur to those skilled in the art. Such changes and other usescan be made without departing from the scope of the invention as setforth in the claims.

We claim:
 1. (canceled)
 2. A medical device adapted to be in contactwith tissue or fluid associated with an organism, comprising: acomponent that contacts the tissue or fluid associated with theorganism; an antimicrobial material associated with the component; acurrent generator connected to the component such that a flow ofantimicrobial ions is created from the antimicrobial material into thetissue or fluid adjacent the component.
 3. The medical device recited byclaim 2, wherein said current generator comprises: a power source inelectrical communication with the antimicrobial material capable ofproducing the antimicrobial ion flow when a current path is establishedthat includes the power source and at least a part of the antimicrobialmaterial; and an insulative material that allows the current path to beestablished by forcing the antimicrobial ion flow into the tissue orfluid adjacent the component.
 4. The medical device recited by claim 2wherein the antimicrobial material is a metal.
 5. The medical devicerecited by claim 2 wherein the antimicrobial material is a metal-dopedmaterial.
 6. The medical device recited by claim 2 wherein the componentis tubular in shape.
 7. The medical device recited by claim 6 whereinthe antimicrobial material is disposed on at least one of the internalor external surface of the component.